Molecular analysis of simple variant translocations in acute promyelocytic leukemia

J. Borrow, J. Shipley, K. Howe, F. Kiely, A. Goddard, D. Sheer, A. Srivastava, A. C. Antony, Asok Antony, F. Mitelman, E. Solomon

Research output: Contribution to journalArticle

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Abstract

The primary cytogenetic abnormality in acute promyelocytic leukemia (APL; FAB M3) is a reciprocal translocation, t(5;17)(q22;q12), which serves to fuse the PML gene on chromosome 15 to the retinoic acid receptor alpha (RARA) gene on chromosome 17. A PML-RARA fusion message transcribed from the der(15) is thought to mediate leukemogenesis. Two APL patients with simple variants of this translocation, t(3;15)(q21;q22) and t(X;15)(p11;q22), have previously been reported who lack cytogenetic involvement of chromosome 17, although their breakpoint positions on chromosome 15 still suggest the involvement of the PML gene. Here we report on a combined analysis by molecular genetics and in situ hybridization of these two patients, in which we wanted to determine whether the PML gene has alternative fusion partners or whether cryptic rearrangement of the RARA locus has occurred instead. A cryptic involvement of RARA was demonstrated in both patients by a combination of Southern analysis, reverse transcription coupled to PCR (RT-PCR), and fluorescence in situ hybridization. The results indicate an absolute requirement for the rearrangement of the RARA gene in the pathogenesis of APL and underline the importance of RARA during normal myeloid differentiation.

Original languageEnglish (US)
Pages (from-to)234-243
Number of pages10
JournalGenes Chromosomes and Cancer
Volume9
Issue number4
StatePublished - 1994

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Acute Promyelocytic Leukemia
Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 17
Genes
Polymerase Chain Reaction
Fluorescence In Situ Hybridization
Cytogenetics
Chromosome Aberrations
Reverse Transcription
In Situ Hybridization
Retinoic Acid Receptor alpha
Molecular Biology

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Borrow, J., Shipley, J., Howe, K., Kiely, F., Goddard, A., Sheer, D., ... Solomon, E. (1994). Molecular analysis of simple variant translocations in acute promyelocytic leukemia. Genes Chromosomes and Cancer, 9(4), 234-243.

Molecular analysis of simple variant translocations in acute promyelocytic leukemia. / Borrow, J.; Shipley, J.; Howe, K.; Kiely, F.; Goddard, A.; Sheer, D.; Srivastava, A.; Antony, A. C.; Antony, Asok; Mitelman, F.; Solomon, E.

In: Genes Chromosomes and Cancer, Vol. 9, No. 4, 1994, p. 234-243.

Research output: Contribution to journalArticle

Borrow, J, Shipley, J, Howe, K, Kiely, F, Goddard, A, Sheer, D, Srivastava, A, Antony, AC, Antony, A, Mitelman, F & Solomon, E 1994, 'Molecular analysis of simple variant translocations in acute promyelocytic leukemia', Genes Chromosomes and Cancer, vol. 9, no. 4, pp. 234-243.
Borrow J, Shipley J, Howe K, Kiely F, Goddard A, Sheer D et al. Molecular analysis of simple variant translocations in acute promyelocytic leukemia. Genes Chromosomes and Cancer. 1994;9(4):234-243.
Borrow, J. ; Shipley, J. ; Howe, K. ; Kiely, F. ; Goddard, A. ; Sheer, D. ; Srivastava, A. ; Antony, A. C. ; Antony, Asok ; Mitelman, F. ; Solomon, E. / Molecular analysis of simple variant translocations in acute promyelocytic leukemia. In: Genes Chromosomes and Cancer. 1994 ; Vol. 9, No. 4. pp. 234-243.
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